학술논문
Chondroitinase improves anatomical and functional outcomes after primate spinal cord injury
Document Type
article
Author
Rosenzweig, Ephron S; Salegio, Ernesto A; Liang, Justine J; Weber, Janet L; Weinholtz, Chase A; Brock, John H; Moseanko, Rod; Hawbecker, Stephanie; Pender, Roger; Cruzen, Christina L; Iaci, Jennifer F; Caggiano, Anthony O; Blight, Andrew R; Haenzi, Barbara; Huie, J Russell; Havton, Leif A; Nout-Lomas, Yvette S; Fawcett, James W; Ferguson, Adam R; Beattie, Michael S; Bresnahan, Jacqueline C; Tuszynski, Mark H
Source
Nature Neuroscience. 22(8)
Subject
Language
Abstract
Inhibitory extracellular matrices form around mature neurons as perineuronal nets containing chondroitin sulfate proteoglycans that limit axonal sprouting after CNS injury. The enzyme chondroitinase (Chase) degrades inhibitory chondroitin sulfate proteoglycans and improves axonal sprouting and functional recovery after spinal cord injury in rodents. We evaluated the effects of Chase in rhesus monkeys that had undergone C7 spinal cord hemisection. Four weeks after hemisection, we administered multiple intraparenchymal Chase injections below the lesion, targeting spinal cord circuits that control hand function. Hand function improved significantly in Chase-treated monkeys relative to vehicle-injected controls. Moreover, Chase significantly increased corticospinal axon growth and the number of synapses formed by corticospinal terminals in gray matter caudal to the lesion. No detrimental effects were detected. This approach appears to merit clinical translation in spinal cord injury.